A Phase 2 interventional study of Ascorbic Acid and Carboplatin in Clonal Cytopenia of Undetermined Significance, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements and Recurrent Diffuse Large B-Cell Lymphoma, sponsored by Mayo Clinic. Recruiting at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-28.
Sponsored by Mayo Clinic · Phase 2, Interventional, and Treatment
This phase II trial studies the effect of ascorbic acid and combination chemotherapy in treating patients with lymphoma that has come back (recurrent) or does not respond to therapy (refractory), clonal cytopenia of undetermined significance and chronic myelomonocytic leukemia (CMML). Ascorbic acid may make cancer cells more sensitive to chemotherapy. Drugs used in chemotherapy, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ascorbic acid and combination chemotherapy may kill more cancer cells.
Arms A, B, C, and D are closed to enrollment.
PRIMARY OBJECTIVES:
I. To determine the overall response rate (ORR) at the end of 2 cycles for intravenous (IV) ascorbic acid (AA) added to standard salvage therapy compared to standard salvage therapy plus normal saline in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who have relapsed within the first 24 months of end of their therapy. [Arms A versus (vs) B] II. To determine the ORR at the end of 2 cycles of AA plus standard salvage chemotherapy in patients with other types of relapsed/refractory lymphomas not eligible for Arms A/B [peripheral T-cell lymphoma (PTCL), double-hit high grade, and Hodgkin lymphoma (HL)]. (Arm C) III. To assess the hematological response rate to treatment with high dose intravenous ascorbic acid (IV AA) for clonal cytopenia of undetermined significance (CCUS) patients. (Arm D) IV. To assess the hematological response rate to treatment with high dose intravenous ascorbic acid (IV AA) for CCUS patients. (Arm E)
SECONDARY OBJECTIVES:
I. To compare the adverse event profile of IV AA added to salvage therapy versus salvage therapy plus IV saline in patients with DLBCL using both the Common Terminology Criteria for Adverse Events (CTCAE) and Patient-Reported Outcomes (PRO)-CTCAE. (Arms A and B) II. To compare the progression-free survival, overall survival, clinical benefit rate (those not progressing), and percentage (%) transplant eligible patients proceeding to transplant of AA added to salvage therapy versus salvage therapy plus IV saline in patients with DLBCL. (Arms A and B) III. To compare the ORR at the end of 4 cycles for those with minor response/stable disease at the end of cycle 2 who proceed to receive the additional 2 cycles of rituximab, dexamethasone, cytarabine and cisplatin (RDHAP) with either AA or normal saline (NS) as previously assigned. (Arms A and B) IV. To evaluate the adverse event profile, rate of febrile neutropenia, overall survival, progression-free survival, and clinical benefit rate of AA added to salvage therapy in patients with relapsed/refractory lymphoma. (Arm C) V. To assess safety/tolerability, transfusion dependency (TD), progression-free survival (PFS), and overall survival (OS) for CCUS patients receiving high dose IV AA. (Arm D) VI. To define CR, complete cytogenetic remission, partial remission, marrow response, and clinical benefit response rates. (Arm E) VII. To determine clinical benefit response rates of erythroid response, platelet response, neutrophil response, spleen response and symptom response as adjudicated by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) total symptom scoring system. (Arm E)
EXPLORATORY OBJECTIVES:
I. Will include baseline AA levels [at Mayo Clinic Research (MCR)] and staining of pre/post treatment biopsies for markers of oxidative stress generation and deoxyribonucleic acid (DNA) methylation. (Arms A, B, and C Correlative Research on blood and tumor tissue) IIa. To assess TET2 activity at baseline, weeks 12, 20, and 52. (Arm D correlative research) IIb. To assess the association between using AA and the hydroxymethylation and methylation status (gene-specific and global changes in 5mC/5hmC level) at baseline and weeks 20 and 52. (Arm D correlative research) IIc. To assess the association between using IV AA and endothelial dysfunction (at baseline, weeks 20, and 52). (Arm D correlative research) IId. To assess the association between using IV AA and the inflammation markers. (Arm D correlative research) IIe. To assess the association between using IV AA and molecular response including clonal dynamics [new mutations and variant allele frequency (VAF)] (at baseline, weeks 20, and 52). (Arm D correlative research)
III. Correlative studies will assess impact on:
IIIa. Somatic mutational allele burdens after 4 cycles of therapy; IIIb. DNA methylation and hydroxymethylation after 4 cycles of therapy; IIIc. Inflammatory cytokines; IIId. Colony forming assay growth and differentiation; IIIe. Methylation at the single colony level; IIIf. Single cell methylation, transcription, and somatic mutations. (Arm E correlative research)
OUTLINE: Patients with DLBCL are randomized to Arms A or B. Patients with other lymphomas are assigned to Arm C. Patients with CCUS are assigned to Arm D. Patients with TET2 mutant CMML are assigned to ARM E.
Arm A (CLOSED): Patients receive ascorbic acid IV on days 1, 3, 5, 8, 10, 12, 15, 17, and 19, and rituximab intravenously (IV), ifosfamide IV, carboplatin IV and etoposide IV on days 1-3. Patients who achieve minor response (MR) or stable disease (SD) after 2 cycles may receive rituximab IV or PO, cisplatin IV or PO, cytarabine IV or PO, and dexamethasone IV or PO. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
ARM B (CLOSED): Patients receive placebo (normal saline) IV on days 1, 3, 5, 8, 10, 12, 15, 17, and 19, and rituximab intravenously IV, ifosfamide IV, carboplatin IV and etoposide IV on days 1-3. Patients who achieve MR or SD after 2 cycles may receive rituximab IV or PO, cisplatin IV or PO, cytarabine IV or PO, and dexamethasone IV or PO. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
ARM C (CLOSED): Patients receive ascorbic acid IV on days 1, 3, 5, 8, 10, 12, 15, 17, and 19. Patients also receive ifosfamide, carboplatin, and etoposide IV or PO, or cisplatin, cytarabine, and dexamethasone IV or PO, or gemcitabine hydrochloride, dexamethasone, and cisplatin IV or PO, or gemcitabine hydrochloride and oxaliplatin IV or PO, or oxaliplatin, cytarabine, and dexamethasone IV or PO according to standard regimen schedule. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve MR or SD after 2 cycles may switch to an alternative chemotherapy regimen.
ARM D (CLOSED): Patients receive ascorbic acid IV three times a week (TIW). Treatments repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
ARM E: Patients receive ascorbic acid IV on days 1, 3 and 5 and decitabine IV over 1 hour or decitabine and cedazuridine PO on days 1-5. Treatment repeats every 35 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 12 cycles may continue decitabine with or without ascorbic acid as long as clinically appropriate. Patients may also take vitamin C PO on days 6-28.
In Arms A, B, and C, patients who achieve complete response (CR), partial response (PR) or MR may undergo stem cell transplantation. Patients additionally, undergo blood sample collection, core needle biopsy, bone marrow aspiration and biopsy, echocardiography (ECHO), positron emission tomography (PET)/ computed tomography (CT) or magnetic resonance imaging (MRI) throughout study.
Patients in ARM D and E undergo peripherally inserted central catheter (PICC) or portacath placement prior to starting treatment, blood sample collection, bone marrow aspiration and biopsy throughout study.
After completion of study treatment, patients are followed up every 3 months, then every 6 months after progressive disease for up to 2 years.
1,868 studies on the registry are indexed under Lymphoma, Large B-Cell, Diffuse; 355 are open to participants now.
This study's planned enrollment of 80 is above the median of 45 across 1,497 interventional studies indexed under Lymphoma, Large B-Cell, Diffuse.
Browse Lymphoma, Large B-Cell, Diffuse studies →Mayo Clinic is the lead sponsor of 3,269 studies on the registry; 672 are open to participants now.
Of its 452 completed or terminated interventional studies of FDA-regulated products, 321 (71%) have results posted.
Counted across the registry records on this site, refreshed daily.
The criteria were revised on the registry on Sep 28, 2026. See what changed
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
-proven lymphomas; relapsed is defined as a relapse that occurred after having a response to the last therapy that lasted > 6 months; refractory is no response or relapse within 6 months; previous biopsies \< 6 months prior to treatment on this protocol will be acceptable
Measurable or assessable disease: is defined as measurable by computed tomography (CT) [dedicated CT or the CT portion of a positron emission tomography (PET)/CT] or magnetic resonance imaging (MRI): to be considered measurable, there must be at least one lesion that has a single diameter of >= 1.5 cm
Arm C eligible for treatment with one of the following standard, every 3 week, platinum-based salvage regimens (with or without monoclonal antibody as appropriate for the disease):
Negative pregnancy test done =\< 7 days prior to registration, for persons of only
(HIV) test done =\< 14 days prior to registration
ARM D: Patients must meet at least 1 of these 3 laboratory criteria to be enrolled:
ARM E PRE-REGISTRATION: No prior CMML directed therapy.
ARM E PRE-REGISTRATION: For a person of child-bearing potential (WOCBP): Must agree to use or take measures to avoid pregnancy during the study. Adequate contraception is defined as follows:
Consistent and correct use of one of the following methods of birth control:
ARM E PRE-REGISTRATION: WOCBP must have a negative serum or urine pregnancy test ≤ 14 days prior to pre-registration. WOCBP will repeat the serum or urine pregnancy test ≤ 7 days prior to the initiation of starting treatment for confirmation of a negative pregnancy.
ARM E PRE-REGISTRATION: Persons who are able to father a child must use contraception during the study and for 3 months after the last treatment dose.
Exclusion Criteria:
Any of the following:
Other active than lymphoma
ARM D: Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
ARM E REGISTRATION: Any of the following because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CD4 count
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients receive ascorbic acid IV on days 1, 3, 5, 8, 10, 12, 15, 17, and 19, and rituximab intravenously IV, ifosfamide IV, carboplatin IV and etoposide IV on days 1-3. Patients who achieve MR or SD after 2 cycles may receive rituximab IV or PO, cisplatin IV or PO, cytarabine IV or PO, and dexamethasone IV or PO. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients additionally, undergo blood sample collection, core needle biopsy, bone marrow aspiration and biopsy, ECHO, PET/CT or MRI throughout study.
Dietary Supplement: Ascorbic Acid · Drug: Carboplatin · Drug: Cisplatin · Drug: Cytarabine · Drug: Dexamethasone · Drug: Etoposide · Drug: Ifosfamide · Other: Laboratory Biomarker Analysis · Other: Questionnaire Administration · Biological: Rituximab · Procedure: Biospecimen Collection · Procedure: Core Biopsy · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Procedure: Echocardiography · Procedure: Positron Emission Tomography · Procedure: Magnetic Resonance Imaging · Procedure: Computed Tomography
Patients receive placebo (normal saline) IV on days 1, 3, 5, 8, 10, 12, 15, 17, and 19, and rituximab intravenously IV, ifosfamide IV, carboplatin IV and etoposide IV on days 1-3. Patients who achieve MR or SD after 2 cycles may receive rituximab IV or PO, cisplatin IV or PO, cytarabine IV or PO, and dexamethasone IV or PO. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients additionally, undergo blood sample collection, core needle biopsy, bone marrow aspiration and biopsy, ECHO, PET/CT or MRI throughout study.
Drug: Carboplatin · Drug: Cisplatin · Drug: Cytarabine · Drug: Dexamethasone · Drug: Etoposide · Drug: Ifosfamide · Other: Laboratory Biomarker Analysis · Other: Placebo Administration · Other: Questionnaire Administration · Biological: Rituximab · Procedure: Biospecimen Collection · Procedure: Core Biopsy · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Procedure: Echocardiography · Procedure: Positron Emission Tomography · Procedure: Magnetic Resonance Imaging · Procedure: Computed Tomography
Patients receive ascorbic acid IV on days 1, 3, 5, 8, 10, 12, 15, 17, and 19. Patients also receive ifosfamide, carboplatin, and etoposide IV or PO, or cisplatin, cytarabine, and dexamethasone IV or PO, or gemcitabine hydrochloride, dexamethasone, and cisplatin IV or PO, or gemcitabine hydrochloride and oxaliplatin IV or PO, or oxaliplatin, cytarabine, and dexamethasone IV or PO according to standard regimen schedule. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve MR or SD after 2 cycles may switch to an alternative chemotherapy regimen. Patients additionally, undergo blood sample collection, core needle biopsy, bone marrow aspiration and biopsy, ECHO, PET/CT or MRI throughout study.
Dietary Supplement: Ascorbic Acid · Drug: Carboplatin · Drug: Cisplatin · Drug: Cytarabine · Drug: Dexamethasone · Drug: Etoposide · Drug: Gemcitabine Hydrochloride · Drug: Ifosfamide · Other: Laboratory Biomarker Analysis · Drug: Oxaliplatin · Other: Questionnaire Administration · Procedure: Biospecimen Collection · Procedure: Core Biopsy · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Procedure: Echocardiography · Procedure: Positron Emission Tomography · Procedure: Magnetic Resonance Imaging · Procedure: Computed Tomography
Patients receive ascorbic acid IV TIW. Treatments repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PICC or portacath placement prior to starting treatment, blood sample collection, bone marrow aspiration and biopsy throughout study.
Dietary Supplement: Ascorbic Acid · Other: Laboratory Biomarker Analysis · Other: Questionnaire Administration · Procedure: Biospecimen Collection · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Procedure: Central Venous Cannula Insertion · Procedure: Portacath Placement
Patients receive ascorbic acid IV on days 1, 3 and 5 and decitabine IV over 1 hour on days 1-5. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 12 cycles may continue decitabine with or without ascorbic acid as long as clinically appropriate. Patients may also take vitamin C PO on days 6-28. Patients undergo PICC or portacath placement prior to starting treatment, blood sample collection, bone marrow aspiration and biopsy throughout study.
Dietary Supplement: Ascorbic Acid · Drug: Decitabine · Procedure: Biospecimen Collection · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Procedure: Central Venous Cannula Insertion · Procedure: Portacath Placement · Drug: Decitabine and Cedazuridine
Given IV
Also known as: 2-(1,2-dihydroxyethyl)-4,5-dihydroxy-furan-3-one, Asorbicap, C Vitamin, C-Long, Ce-Vi-Sol, Cecon, Cenolate, Cetane, Cevalin, L-Ascorbic Acid, VIT C, Vitamin C, Vitamin-C
Given IV or PO
Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo, JM8
Given IV or PO
Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin
Given IV or PO
Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453
Given IV or PO
Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex
Given IV or PO
Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP 16213, VP-16-213, VP16, VP-16
Given IV or PO
Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, Gemzar, LY-188011, LY188011
Given IV or PO
Also known as: Asta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942
Correlative studies
Given IV or PO
Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669
Given normal saline IV
Ancillary studies
Given IV
Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Riabni, Rituxan, Rituximab ABBS, Rituximab ARRX, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, Rituximab PVVR, Rituximab-abbs, Rituximab-arrx, Rituximab-pvvr, RTXM83, Ruxience, Truxima, Ikgdar, Mabtas
Given IV
Also known as: Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine
Undergo blood sample collection
Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo core needle biopsy
Also known as: BIOPSY, CORE, CORE CNB, Core Needle, Core Needle Biopsy, Needle Biopsy
Undergo bone marrow aspiration and biopsy
Undergo bone marrow aspiration and biopsy
Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow
Undergo ECHO
Also known as: EC, ECHO
Undergo PET/CT
Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), positron emission tomography scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT
Undergo MRI
Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, nuclear magnetic resonance imaging, Structural MRI, sMRI
Undergo PICC placement
Also known as: Central venous catheter, Central Venous Catheter Placement
Undergo portacath placement
Also known as: Port-a-cath Placement
Undergo PET/CT
Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT SCAN, tomography
Given PO
Also known as: ASTX 727, ASTX-727, ASTX727, C-DEC, CDA Inhibitor E7727/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Tablet, DEC-C, Inaqovi, Inqovi
Overall response rate (ORR) (Arms A and B)
Defined as an objective status of complete response (CR) or partial response (PR) evaluated by Response Evaluation Criteria in Lymphoma (RECIL) criteria after 2 courses of treatment in all arms. Will be compared between the two arms. The proportion of successes will be estimated in each arm by the number of successes divided by the total number of evaluable patients. Exact binomial ninety-five percent confidence intervals for the true success proportion will be calculated in each arm. For the diffuse large B-cell lymphoma (DLBCL) arms, comparison of overall response rates between the two treatment groups will be performed using a one-sided chi-square test at significance level 0.10.
Time frame: Up to 2 years
ORR (Arm C)
Defined as an objective status of CR or PR evaluated by RECIL criteria after 2 cycles of treatment. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial ninety-five percent confidence intervals for the true success proportion will be calculated in each arm.
Time frame: Up to 2 years
Hematologic response (HI) rate (Arm D)
Defined as an objective status of HI-E (minor or major response), HI-P, or HI-N evaluated by Myelodysplastic Syndrome International Working Group (IWIG) 2018 criteria at 20 weeks. Exact binomial ninety-five percent confidence intervals for the true success proportion will be calculated in each arm.
Time frame: At 20 weeks
Overall Response Rate (ORR) in Arm E
Defined as an objective status of complete remission, complete cytogenetic remission, partial remission, bone marrow response, or clinical benefit after 4 cycles of therapy as defined by the 2015 IWG myelodysplastic syndrome/ myeloproliferative neoplasm response criteria.
Time frame: At completion of cycle 4 (each cycle is 21 days)
Clinical benefit rate (Arms A, B, and C)
Will be estimated in each arm by the number of patients who achieve a CR, PR, minor response (MR), or stable disease (SD) on the cycle 2 response assessment divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success rate will be calculated. The clinical benefit rate will be compared between the DLBCL arms using the chi-square test (or Fisher's exact test if the data in the contingency table is sparse).
Time frame: Up to 2 years
Overall survival
The distribution of overall survival will be estimated in each arm using the method of Kaplan-Meier. In the DLBCL arms, the comparison of overall survival between the two treatment arms will be based on the log-rank test.
Time frame: From registration to death due to any cause, assessed up to 2 years
Progression-free survival
The distribution of progression-free survival will be estimated in each arm using the method of Kaplan-Meier. In the DLBCL arms, the comparison of progression-free survival between the two treatment arms will be based on the log-rank test.
Time frame: From date of first treatment to the earliest date of documentation of disease progression or death due to any cause, assessed up to 2 years
Percent of transplant eligible patients proceeding to transplant (Arms A, B and C)
Will be estimated in each arm by the number of patients proceeding to transplant divided by the total number of patients who were considered transplant eligible. Exact binomial 95% confidence intervals for the true success rate will be calculated. The rate will be compared between the DLBCL arms using the chi-square test (or Fisher's exact test if the data in the contingency table is sparse).
Time frame: Up to 2 years
Transfusion dependency (Arm D)
Transfusion dependency will be summarized descriptively. The number of patients transfusion dependent at baseline and during follow-up will be summarized.
Time frame: Up to 2 years
Incidence of adverse events
Assessed using Common Terminology Criteria for Adverse Events (CTCAE). The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. In the DLBCL arms, the overall adverse event rates for Grade 3 or higher hematologic and non-hematologic adverse events at least possibly related to treatment will be compared between the two treatment groups using the chi-square test (or Fisher's exact test if the data in the contingency table is sparse). The rate of febrile neutropenia will be evaluated in each arm.
Time frame: Up to 2 years
Incidence of adverse events
Assessed using Patient Reported Outcomes (PRO)-CTCAE (Arms A and B). PRO-CTCAE scores range from 0-4, with corresponding response choices for frequency (Never / Rarely / Occasionally / Frequently / Almost constantly), for severity (None / Mild / Moderate / Severe / Very severe) and interference (Not at all / A little bit / Somewhat / Quite a bit / Very much). The scores for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. PRO-CTCAE scores will be compared between the two treatment groups using the chi-square test (or Fisher's exact test if the data in the contingency table is sparse).
Time frame: Up to 2 years
Continued salvage therapy beyond cycle 2 (Arm A, B and C)
Will be assessed by evaluating the number of patients who achieve an improved response after cycle 4 compared to the cycle 2 assessment in patients who received additional cycles of ascorbic acid/placebo added to salvage therapy beyond cycle 2. In addition, the number of patients who changed salvage therapies after cycle 2 will be assessed. This analysis will be primarily descriptive.
Time frame: Up to 2 years
Clinical benefit rate (Arm E)
The rates of complete response, complete cytogenetic remission, partial remission, marrow response, and clinical benefit will be estimated by the number of patients with each response type divided by the number of evaluable patients.
Time frame: Up to 2 years
Hematologic response rate in Arm E
The rates of erythroid response, platelet response, neutrophil response, spleen response and symptom response will be estimated by the number of patients with each response type divided by the number of evaluable patients.
Time frame: Up to 2 years
Biomarker analysis on blood and tissue (Arms A, B, and C)
Will consider the correlative research exploratory.
Time frame: Baseline up to 2 years
Biomarker analysis (Arm D)
Variant allele frequency (VAF), biomarkers levels from Olink study, values of the cytokines, endothelial dysfunction, inflammation markers and levels of 5mc/5hmc will be measured at baseline, after completion of treatment (at 20 weeks), and at one-year post-registration. Values will be summarized graphically and descriptively at each time point and changes across time will be explored. Due to small sample size, these correlative analyses will be considered exploratory.
Time frame: Baseline up to 2 years
Molecular response (Arm D)
Defined as a 2 standard deviation reduction in VAF from baseline VAF. Exact binomial 95% confidence intervals for the true success rate will be calculated.
Time frame: Up to 2 years
TET2 activity (Arm D)
Values will be summarized graphically and descriptively at each time point and changes across time will be explored.
Time frame: At baseline and weeks 12, 20, 52
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From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drugs tested here: Ascorbic Acid · Carboplatin · Cisplatin · Cytarabine · Dexamethasone · Etoposide · Ifosfamide · Rituximab
Lymphoma, Large B-Cell, Diffuse →